The Safety of Key Inhaled and Intravenous Drugs in Pediatrics (SAFEKIDS): an update.
The Safety of Key Inhaled and Intravenous Drugs in Pediatrics (SAFEKIDS): an update.
复制标题
儿科关键吸入和静脉药物的安全性 (SAFEKIDS)：更新。
DOI：
10.1213/ane.0b013e3181d5a656
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发表时间：
2010
影响因子：
5.7
通讯作者：
P. Davis
中科院分区：
文献类型：
--
作者：
M. Durieux;P. Davis
过去几年报道的临床前研究结果引起了人们的担忧，即儿科实践中常规使用的一些麻醉剂可能并不像我们过去认为的那样无害。在啮齿类动物中，挥发性药物和注射药物（特别是联合使用时）已被证明会在发育中的大脑中诱导严重的细胞凋亡，与以后生活中的行为变化有关。最近一期的《麻醉与镇痛》杂志上有几篇文章对这一主题进行了综述。这些动物数据已经得到证实，扩大，似乎坚实。当然，最大的问题是，在接受麻醉的晚期胎儿或幼儿中是否会发生类似的影响。这是一个非常难研究的问题，原因有几个。首先，有时间因素：从早期麻醉暴露到（比方说）高中表现的差异之间会经过许多年。这使得设计一个真正的前瞻性研究与长期随访几乎是不可能的。第二，有很多混杂变量。几乎所有接受麻醉的儿童都是因为他们有医疗问题。因此，有可能，甚至很可能，潜在的医疗问题可能是导致认知能力随后变化的原因，而不是暴露于麻醉药物。理清这件事很难。同样，大多数接受麻醉的儿童也会接受手术。如何将麻醉药物的作用与手术的作用和围手术期经历的创伤分开？第三，单次麻醉对认知功能的影响可能是适度的。我们如何将这种温和的影响与随后几年经历的无数生理和病理损伤区分开来，特别是因为认知功能显示出如此多的主体间差异？第四，神经病理学效应（神经细胞凋亡）不能用现有的成像技术在人类中进行研究。这些问题和其他问题使得麻醉诱导的神经毒性在年轻人中的临床研究成为一项艰巨的任务。但临床前数据不容忽视。美国食品药品监督管理局（FDA）意识到，一旦临床前数据可用，就需要进行进一步的研究，并制定了一项计划，涉及额外的临床前工作（特别是灵长类动物）和开发支持临床试验的结构。FDA还认识到，这种复杂性的问题需要公共和私人来源的智力和财政支持。因此，他们与国际麻醉研究学会（IARS，出版麻醉与镇痛的母组织）建立了公私合作伙伴关系（PPP）。这项合作被称为“SAFEKIDS”（儿科关键吸入和静脉注射药物的安全性），于2009年3月13日宣布。它的官方目标是“解决有关儿童安全使用麻醉剂和镇静剂的科学信息的主要空白”。去年11月，在FDA白色橡树校区（马里兰州银泉）召开了第一次SAFEKIDS科学研讨会，讨论进展情况。本文概述了这次会议的一些主要成果。
Preclinical findings reported over the past years have raised worries that some of the anesthetics used routinely in pediatric practice may not be as innocuous as we used to think. In rodents, volatile as well as injected drugs (particularly when used in combination) have been shown to induce profound apoptosis in the developing brain, associated with behavioral changes later in life. Several articles in a recent issue of Anesthesia & Analgesia have reviewed this topic. These animal data have been confirmed, expanded on, and seem solid. The big question, of course, is whether similar effects might occur in late-term fetuses or young children receiving anesthesia. This is an exceedingly difficult question to study, for several reasons. First, there is the time factor: many years will pass between early anesthesia exposure and (let’s say) differences in performance in high school. This makes designing a truly prospective study with long-term follow-up almost impossible. Second, there are lots of confounding variables. Almost all children who undergo anesthesia do so because they have a medical problem. Therefore, it is possible, and even likely, that the underlying medical problem might be responsible for subsequent changes in cognitive performance, rather than the exposure to anesthetic drugs. Sorting this out is difficult. Similarly, most children receiving anesthesia also undergo surgery. How does one separate the effects of anesthetic drugs from the effects of surgery and the trauma of the perioperative experience? Third, the effect of a single exposure to anesthesia on cognitive function is likely modest. How can one separate that modest effect from the myriad of physiologic and pathologic insults experienced during the subsequent years, particularly because cognitive function shows so much intersubject variability anyway? Fourth, the neuropathologic effects (neuroapoptosis) cannot be studied in humans with existing imaging techniques. These and other problems make the clinical study of anesthetic-induced neurotoxicity in the young a daunting undertaking. But the preclinical data cannot be ignored. The Food and Drug Administration (FDA) realized the need for further research as soon as the preclinical data became available and developed a program involving additional preclinical work (particularly in primates) and development of a structure to support clinical trials. The FDA also understood that a problem of this complexity would require intellectual and financial support from public as well as private sources. Therefore, they formed a public-private partnership (PPP) with the International Anesthesia Research Society (IARS, the parent organization that publishes Anesthesia & Analgesia). This partnership, dubbed “SAFEKIDS” (Safety of Key Inhaled and IV Drugs in Pediatrics), was announced on March 13, 2009.* Its official goal is “to address major gaps in scientific information concerning the safe use of anesthetics and sedatives in children.” Last November, the first SAFEKIDS scientific workshop was convened at the FDA White Oak campus (Silver Spring, MD) to discuss the progress. This article summarizes some of the main outcomes of this meeting.